Antipsychotic-induced vacuous chewing movements and extrapyramidal side effects are highly heritable in mice.

Pharmacogenomics is yet to fulfill its promise of manifestly altering clinical medicine. As one example, a predictive test for tardive dyskinesia (TD) (an adverse drug reaction consequent to antipsychotic exposure) could greatly improve the clinical treatment of schizophrenia but human studies are equivocal. A complementary approach is the mouse-then-human design in which a valid mouse model is used to identify susceptibility loci, which are subsequently tested in human samples. We used inbred mouse strains from the Mouse Phenome Project to estimate the heritability of haloperidol-induced activity and orofacial phenotypes. In all, 159 mice from 27 inbred strains were chronically treated with haloperidol (3 mg kg(-1) per day via subdermal slow-release pellets) and monitored for the development of vacuous chewing movements (VCMs; the mouse analog of TD) and other movement phenotypes derived from open-field activity and the inclined screen test. The test battery was assessed at 0, 30, 60, 90 and 120 days in relation to haloperidol exposure. As expected, haloperidol caused marked changes in VCMs, activity in the open field and extrapyramidal symptoms (EPS). Unexpectedly, factor analysis demonstrated that these measures were imprecise assessments of a latent construct rather than discrete constructs. The heritability of a composite phenotype was ∼0.9 after incorporation of the longitudinal nature of the design. Murine VCMs are a face valid animal model of antipsychotic-induced TD, and heritability estimates from this study support the feasibility of mapping of susceptibility loci for VCMs.

Extensor tendon rehabilitation a prospective trial comparing three rehabilitation regimes.

Forty-two patients with 46 complete extensor tendon injuries were prospectively allocated to one of three rehabilitation regimes: static splintage; interphalangeal joint mobilization with metacarpophalangeal joint immobilization or; the "Norwich" regime. All 42 patients were operated on by one surgeon and assessed by one hand therapist. At 4 weeks the total active motion in the static splintage group was significantly reduced but by 12 weeks there was no difference between the regimes. There was no difference in total active motion between the repaired and uninjured hand at 12 weeks, with all patients achieving good or excellent results. However, grip strength at 12 weeks was significantly reduced compared to the uninjured hand after static splintage. There was no difference in hand therapy input between the regimes.

A prospective randomised clinical trial of the intra-operative use of 5-fluorouracil on the outcome of dupuytren's disease.

5-Fluorouracil reduces proliferation rates of fibroblasts, myofibroblast differentiation and contractility of ocular fibroblasts in vitro. This double-blind randomized clinical trial assesses whether intra-operative topical treatment with 5-fluorouracil reduces the recurrence rate after limited excision of Dupuytren's tissue. Patients with two-digit disease were randomized to having 5-fluorouracil (25mg/ml) treatment for 5 minutes on one digit and placebo on the other. Fifteen patients were enrolled with 18 months follow-up. There were no peri-operative complications. Wound healing was not delayed and there was no deterioration in the flexion deformity of the 5-fluorouracil treated digits. Patients were subsequently assessed by joint angle measurement at 3, 6, 12 and 18 months. There was no significant difference between control and 5-fluorouracil treated digits.

A prospective review of open central slip laceration repair and rehabilitation.

A prospective review was carried out to evaluate the outcome of surgically repaired open central slip (zone III) injuries which were treated with 3 weeks of proximal interphalangeal joint immobilization within a cylinder splint and then with 3 weeks of controlled mobilization within a Capener coil splint. Thirty-one fingers in 27 patients were assessed by the same independent therapist. All fingers achieved an excellent or good recovery with a mean proximal interphalangeal joint flexion of 94 degrees (range 70-110 degrees) and a mean distal interphalangeal joint flexion of 57 degrees (range 30-81 degrees). Extension deficits of the proximal interphalangeal joint were noted in five fingers (mean 6 degrees, range 3-15 degrees). The results show that a combination of immobilization and controlled mobilization is an effective rehabilitation regime for surgically repaired open central slip injuries.

An alternative splinting and rehabilitation protocol for metacarpophalangeal joint arthroplasty in patients with rheumatoid arthritis.

This prospective study was completed to establish results obtained using a static splinting regimen as an alternative to the dynamic extension splint. Fifteen patients with rheumatoid arthritis, who had undergone metacarpophalangeal (MCP) joint arthroplasties and a postoperative rehabilitation program of alternating MCP joint flexion and extension static splints, were assessed pre-operatively and reviewed postoperatively. Total active arc of MCP joint motion and ulnar deviation were measured, and an activities-of-daily-living questionnaire was completed by each patient at 19 months (mean) postoperatively. Mean total active arc of MCP joint motion showed statistical improvement from 21.6 degrees (range, 5 degrees-60 degrees) pre-operatively to 47.2 degrees (range, 15 degrees-84 degrees) postoperatively. The little finger gained the most improvement, with a 50.2 degree arc, showing that this regimen does not compromise flexion gains at this joint. Ulnar deviation improved from a mean of 30.4 degrees (range, 5 degrees-65 degrees) pre-operatively to 9.7 degrees (range, 0 degrees-30 degrees) postoperatively. These initial results reinforce the clinical impression that this alternating static splint regimen can be used as an effective alternative to the dynamic extension splint.